An Open-Label Study of Apabetalone in Covid Infection

An Open-Label Study to Assess the Safety and Effect on Clinical Course and Key Biomarkers of Oral Apabetalone in Hospitalized Subjects With Covid-19 Infection in Addition to Standard of Care (SOC)

The primary objective of the study is to evaluate the safety and effect on clinical course of oral apabetalone in hospitalized subjects with Covid-19 infection

Study Overview

• Status: Terminated
• Conditions: COVID-19 Infection
• Intervention / Treatment: Other: Standard of care; Drug: Apabetalone

Detailed Description

Primary Objective:

The primary objective of the study is to evaluate the safety and effect on clinical course of oral apabetalone in hospitalized subjects with Covid-19 infection

Secondary Objectives:

To evaluate the effect of apabetalone on biomarkers of inflammation (interleukin [IL]-6, IL-8, tumor necrosis factor [TNF]-α and C-reactive protein [CRP]) To evaluate the effect of apabetalone on key virus-related biomarkers including ACE2, serine protease inhibitor Clade A Member 8 (SERPINA8), angiotension (Ang) II and Ang (1-7) and others within the renin-angiotensin system (RAS) To evaluate the effect of apabetalone on clinical laboratory parameters including white blood cell (WBC) count, platelet count, D-Dimer, ferritin and clotting time in hospitalized subjects with Covid-19 infection To evaluate the effect of apabetalone cardiac and renal biomarkers including N-terminal pro B-type natriuretic peptide (NT-proBNP), troponin and Cystatin C To evaluate changes in viral levels measured via oropharyngeal or nasopharyngeal swabs To evaluate the effect of apabetalone on rate of admission to ICU, need for mechanical ventilation/ECMO, and death To evaluate the safety of apabetalone in hospitalized subjects with Covid-19 Infection

• Study Type: Interventional
• Enrollment (Actual): 1
• Phase: Phase 2; Phase 3

Contacts and Locations

Study Locations

• Canada
  • Alberta
    • Edmonton, Alberta, Canada, AB T6G 2N2
      • University of Alberta

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Provide informed consent before participation in the study.
2. Aged ≥18 years
3. Hospital admission with symptoms suggestive of COVID-19 infection
4. Ten days or less since the onset of symptoms
5. Virological confirmation of SARS-CoV2 infection by reverse transcriptase PCR (RT- PCR) according to Center for Disease Control and Prevention (CDC) guidelines within the previous 72 hours
6. Subjects showing bilateral pulmonary infiltrates on chest imaging
7. Saturation of oxygen (SpO2) by pulse oximetry <94% on room air at sea level.

8. Female subjects must meet one of the following:

   • If of childbearing potential, female subjects must have a negative urine pregnancy test at screening and must also be willing to practice total abstinence or to use an approved (non-hormonal) form of birth-control throughout the study treatment phase and up to 28 days after the last study drug dose if randomized to apabetalone." -OR-
   • Meet at least one of the following criteria:
   • Be postmenopausal, defined as having been amenorrheic for at least 2 years
   • Have had a hysterectomy or a bilateral oophorectomy

Exclusion Criteria:

1. Subjects with SpO2 >94% on room air using pulse oximetry and without bilateral infiltrates on chest imaging
2. Subjects requiring mechanical ventilation or extracorporeal membrane oxygenation
3. Patients with Stage 5 CKD receiving renal replacement therapy with either hemodialysis or peritoneal dialysis, renal transplant or with eGFR <15 mL/min/1.73 m2.
4. Patients with prior transplantations of organs or bone marrow.
5. Patients with unstable cardiac condition including heart attack, stroke, uncontrolled atrial fibrillation or a major cardiac procedure within 3 months as assessed by the investigator.
6. New York Heart Association Class IV congestive heart failure.
7. Evidence of cirrhosis from liver imaging or biopsy, a history of hepatic encephalopathy, esophageal or gastric varices, active hepatitis, or prior porta-caval shunt procedure.
8. ALT or AST >5 x ULN on admission laboratory assessment.
9. Total bilirubin >2 x ULN on admission laboratory assessment.
10. Have received any live attenuated vaccine within 90 days at dosing.
11. Known human immunodeficiency virus positive patients.
12. Chronic use of oxygen therapy at home
13. Have participated in a clinical study and received any investigational medication within the last 30 days preceding Visit 1 (Screening).
14. Subjects whose safety may be compromised by study participation
15. Are not, in the opinion of the investigator, able or willing to comply with the protocol.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: Standard of Care; All subjects will receive SOC during their hospital admission. This will include daily vital signs, WHO Ordinal Scale assessment and adverse events. On Days 3, 5, 7 and 11, hematology, chemistry, oropharyngeal or nasopharyngeal swabs for Covid-19 viral levels and biomarkers samples the same as at the screening visit will be taken if the patient remains in hospital.	Other: Standard of care; Standard of Care
Experimental: Standard of Care plus apabetalone; All subjects will receive SOC during their hospital admission. This will include daily vital signs, WHO Ordinal Scale assessment and adverse events. On Days 3, 5, 7 and 11, hematology, chemistry, oropharyngeal or nasopharyngeal swabs for Covid-19 viral levels and biomarkers samples the same as at the screening visit will be taken if the patient remains in hospital. For the apabetalone cohort, treatment will be administered BID with meals.	Other: Standard of care; Standard of Care; Drug: Apabetalone; Apabetalone 100mg BID

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The primary endpoint of the study is the change in WHO Ordinal Scale for Clinical Improvement at Day 14	WHO Ordinal Scale for Clinical Improvement, 8 point scale, 0 = no clinical or virological evidence of infection	Change in WHO Ordinal Scale for Clinical Improvement at Day 14

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in WHO Ordinal Scale for Clinical Improvement at Day 28	WHO Ordinal Scale for Clinical Improvement, 8 point scale, 0 = no clinical or virological evidence of infection	Study Day 28
Biomarkers of inflammation Interleukin-6	Interleukin-6 is a biomarker of inflammation	Study Day 28
Total time of hospitalization	Total time of hospitalization	through study completion, an average of 28 days
Biomarkers of inflammation Interleukin-8	Interleukin-8 is a biomarker of inflammation	Study Day 28
Biomarkers of inflammation Tumor Necrosis Factor alpha	Tumor Necrosis Factor alpha is a biomarker of inflammation	Study Day 28

Collaborators and Investigators

• Sponsor: Resverlogix Corp

Study record dates

Study Major Dates

• Study Start (Actual): January 14, 2022
• Primary Completion (Actual): June 22, 2022
• Study Completion (Actual): June 22, 2022

Study Registration Dates

• First Submitted: May 5, 2021
• First Submitted That Met QC Criteria: May 18, 2021
• First Posted (Actual): May 20, 2021

Study Record Updates

• Last Update Posted (Estimated): November 17, 2023
• Last Update Submitted That Met QC Criteria: November 14, 2023
• Last Verified: November 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Respiratory Tract Infections; Respiratory Tract Diseases; Pneumonia, Viral; Pneumonia; Lung Diseases; Disease Attributes; COVID-19; Infections; Communicable Diseases
• Other Study ID Numbers: RVX222-CS-023

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No